* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Bulletin de la Societe Chimique de France, 1955, p. 1614
2
[ 1003-31-2 ]
[ 7697-37-2 ]
[ 108-24-7 ]
[ 16689-02-4 ]
[ 42137-24-6 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1955, p. 1614
3
[ 42137-24-6 ]
[ 73781-74-5 ]
Yield
Reaction Conditions
Operation in experiment
41%
Stage #1: With hydrogen In 1,4-dioxane; ethyl acetate for 16 h; Stage #2: for 24 h;
Step 3 4-aminothiophene-2-carbonitrile (3); [0172] Nitrile 2 (100 mg, 0 65 mmol ) in EtOAc (4 mL) and dioxane (0 2 mL) and 5percent Pd/C (77 mg) were placed under hydrogen atmosphere After 16 hours 10percent Pd/C Degussa wet catalyst (30 mg) was added and the mixture was stirred under 1 atm of hydrogen for another 24h The catalyst was filtered over celite and the filtrate was concentrated under vacuum and purified by column chromatography eluting with 20-30percent EtOAc/hexanes giving amine 3 in 41 percent LRMS (ESI) calc 124 2, found 125 1 (MH)+
(c) 4-nitro-2-thiophenecarboxylic acid. A mixture of <strong>[42137-24-6]4-nitro-2-cyanothiophene</strong> (1.5 g; 0.1 mol) in 20 ml of concentrate hydrochloric acid is heated for two hours. As hydrolysis proceeds the reactant goes into solution. The desired product precipitates from the reaction mixture by cooling; m.p. 152-154C (water).
(b) 4-nitro-<strong>[1003-31-2]2-cyanothiophene</strong> To a solution of <strong>[1003-31-2]2-cyanothiophene</strong> (10.9 g; 0.1 mol) in 25 ml of acetic anhydride (t=10 C.) are added 9 ml of fuming nitric acid (d=1.49 g/ml). The temperature is kept under control. When the reaction is complete the reaction mixture is poured into ice, the precipitate is filtered, dried, dissolved in 40 ml of ethyl alcohol, and crystallized up to constant melting point (102 C.); Yield, 30%.
In ethanol; acetic anhydride;
(b) 4-nitro-<strong>[1003-31-2]2-cyanothiophene</strong>. To a solution of <strong>[1003-31-2]2-cyanothiophene</strong> (10.9 g; 0.1 mol) in 25 ml of acetic anhydride (t = 10C) are added 9 ml of fuming nitric acid (d = 1.49 g/ml). The temperature is kept under control. When the reaction is complete the reaction mixture is poured into ice, the precipitate is filtered, dried, dissolved in 40 ml of ethyl alcohol, and crystallized up to constant melting point (102C); Yield, 30%.
1.69 g (15%)
With nitric acid; In acetic anhydride; acetic acid;
A. 2-Cyano-4-nitrothiophene (749Ai) & 2-Cyano-5-nitrothiophene (749Aii) Fuming nitric acid (21 mL) was slowly added to glacial acetic acid (105 mL) and the mixture was then cooled in an ice-bath. <strong>[1003-31-2]2-Cyanothiophene</strong> (7.98 g, 73.1 mmol) was dissolved in 20 mL of acetic anhydride and added dropwise to the above acid mixture such that the temperature did not exceed 25 C. Upon completion of the addition, the reaction mixture was warmed to 22 C. and stirred for 48 h. The reaction was poured over 400 mL of ice and extracted with 200 mL of diethylether. The ether layer was isolated, washed with water, followed by brine and dried over MgSO4. Filtration and concentration in vacuo gave a sticky, orange residue which was purified by column chromatography using 1:1 hexanes/methylene chloride as the eluent to give 1.69 g (15%) of compound 749Ai as a white solid and 1.71 g (15%) of compound 749Aii as a yellow crystalline substance.
With pyridine; hydroxylamine hydrochloride; acetic anhydride; at 95℃; for 2h;
Step 2 4-niotatrothiotaophene-2-carboniotatpile (2); [0171] Acetic anhydride (1 2 mL) was added to a mixture of aldehyde 1 (314 3 mg, 2 00 mmol) and hydroxylamine hydrochloride (277 6 mg, 4 00 mmol) in pyridine (1 5 mL) pre- <n="49"/>heated at 950C according to the procedure of M Bobosikova et al (J Chem Soc , Perkin Trans I, 2001 , 680-689) After 2 h at 950C the mixture was cooled and poured over ice and the precipitate was filtered out and allowed to air dry Nitrile 2 was obtained in 68percent yield as beige solid 1H NMR (CDCI3) delta(ppm) 8 51 (s, 1 H), 8 14 (s, 1 H)
Step 3 4-aminothiophene-2-carbonitrile (3); [0172] Nitrile 2 (100 mg, 0 65 mmol ) in EtOAc (4 mL) and dioxane (0 2 mL) and 5% Pd/C (77 mg) were placed under hydrogen atmosphere After 16 hours 10% Pd/C Degussa wet catalyst (30 mg) was added and the mixture was stirred under 1 atm of hydrogen for another 24h The catalyst was filtered over celite and the filtrate was concentrated under vacuum and purified by column chromatography eluting with 20-30% EtOAc/hexanes giving amine 3 in 41 % LRMS (ESI) calc 124 2, found 125 1 (MH)+
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